Following rhythm guitarist Izzy Stradlin’s decision to abruptly quit the band, during Use Your Illusion Tour in 1991, citing a combination of Axl Rose’s personal behavior (he would consistently delay the start of shows by hours at a time) and his mismanagement of the band and difficulties being around Slash, Sorum, and McKagan due to his new-found sobriety and their continuing alcohol and substance addictions, Clarke was chosen as his replacement, playing out the rest of gigs of the tour which lasted until 1993. His first show with the band was December 5, 1991 in Worcester, MA, USA.

On November 23, 1993, Guns N’ Roses released a collection of punk and glam rock covers entitled “The Spaghetti Incident?” where many of the tracks were recorded with original Guns N’ Roses guitarist Izzy Stradlin during the Use Your Illusion I and II sessions and then were later re-recorded by Clarke.

Following the end of the Use Your Illusion Tour in 1993, Guns N’ Roses guitarist Slash began recording demos of material that he had written during the tour, at his home studio with bandmate Matt Sorum. Clarke and Alice in Chains bassist Mike Inez soon started to come around to jam with them. They eventually recorded twelve demo songs. Eric Dover, live guitarist for Jellyfish, successfully auditioned to become the group’s singer. Slash and Dover wrote the lyrics for all the tracks, except “Monkey Chow” which was contributed by Clarke and “Jizz da Pit” which is an instrumental written by both Slash and Inez. The album was released by Geffen Records in February 1995 charting at No. 70 on the Billboard 200. For the tour in support of the album, James LoMenzo and Brian Tichy, both members of Zakk Wylde’s solo band, joined the band to replace Inez and Sorum who could not tour with the group due to other commitments. With Guns N’ Roses regrouping to record a new album, Snakepit disbanded with Clarke resuming his solo career, releasing his second album The Hangover in 1997.

In 1994, he released his debut solo album Pawnshop Guitars on Virgin Records which featured contributions from several of his close friends. Ryan Roxie (Alice Cooper) on guitar, Will Effertz on Bass and Marc Danzeisen (Riverdogs, Little Caesar) Drums and backing vocals, also including all the then members of Guns N’ Roses. It went gold in Argentina.

He formed the band Col. Parker with ex-Stray Cat Slim Jim Phantom and former touring additional GN’R keyboardist Teddy “Zig Zag” Andreadis, releasing the album Rock N Roll Music in 2001.

In 2002 Clarke worked with Nancy Sinatra on her album California Girl and a year later joined Heart on their national tour.

In addition, he made a guest appearance on the L.A. Guns album Shrinking Violet, which he also produced. Clarke also produced The Bronx’s self-titled album released in 2003 and Girlsplayboys debut album From Ritual to Romance in 2006, and L.A. Guns’ 2001 album Man in the Moon.

In 2006, Mötley Crüe drummer, Tommy Lee, formed Supernova with Clarke on guitars and former Metallica bassist Jason Newsted. The band used the TV show Rockstar to find a new lead singer. Lukas Rossi was chosen as their lead singer. However, there was already a band from California called Supernova. On June 26, 2006, the California band filed a federal lawsuit and on September 12, 2006, U.S. District Judge John A. Houston in San Diego ruled in favor of the original Supernova, granting their request for a preliminary injunction. The injunction stopped the band from Rock Star: Supernova from “performing rock and roll music, or recording, or selling rock and roll music recordings under the same name, pending a trial of this action on its merits, or until otherwise ordered by the court.” The band renamed itself Rock Star Supernova.

In 2007 he released a best of album featuring tracks from all of his solo albums as well as two songs from the Col. Parker project and a rerecording of the song “Black”, featuring vocals by Rock Star: Supernova runner-up Dilana.

In July 2008 Gilby Clarke played at the G-TARanaki Guitar Festival in New Zealand. His solo band included bassist Muddy Stardust and drummer Dennis Morehouse. He then toured North America as part of the Rock n’ Roll Fantasy Camp.

Clarke reunited with Guns N’ Roses members Slash, Steven Adler, Matt Sorum and Duff McKagan, during the live performance, at the band’s Rock and Roll Hall of Fame induction on April 14, 2012. Clarke himself was not inducted as part of the band.